Monday, June 19, 2017

PRION 2017 P20 Descriptive epidemiology of human prion diseases in Japan: a prospective 16-year surveillance study

Japan Prion Disease Increasing Annually to 2.3 patients per 1 million populations in 2014

PRION 2017 P20 Descriptive epidemiology of human prion diseases in Japan: a prospective 16-year surveillance study. 

Ryusuke Ae1, Yosikazu Nakamura1, Ichiro Takumi2', Nobuo Sanjo3, Tetsuyuki Kitamoto4, Masahito Yamada5, Tsuyoshi Hamaguchi5, Tadashi Tsukamoto6, Hidehiro Mizusawa6 

1Division of Public Health, Center for Community Medicine, Jichi Medical University, ,Japan, 2Department of Neurosurgery, Nippon Medical School Musashi Kosugi Hospital, , Japan, 3Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, , Japan, 4Department of Neurological Science, Tohoku University Graduate School of Medicine, ,Japan, 5Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, , Japan, 6National Center Hospital, National Center of Neurology and Psychiatry, , Japan 

Introduction: A nationwide registration system for human prion diseases (hPrDs) has been operating in Japan since 1999. We aimed to reveal the epidemiologic features of hPrDs in Japan by analyzing this 16-year database. 

Methods: Information on patients suspected of having hPrDs was obtained from three sources: (1) the government's Intractable Disease Treatment Research Program, (2) the government's Infectious Diseases Control Law, and (3) requests from physicians to the Creutzfeldt-Jakob Disease (CJD) Surveillance Committee for genetic or cerebrospinal fluid analysis through Tohoku University and Nagasaki University, respectively. We analyzed data from all patients suspected of having hPrDs who were registered by the CJD Surveillance Committee between April 1999 and September 2016. All referrals were assessed using the World Health Organization case definition for hPrDs. 

Results: During the surveillance period, 5711 suspected patients were identified, and 2917 were confirmed as having hPrDs, including 1161 males (43%) and 1656 females (57%). Annual incidence of hPrDs has tended to increase since 1999, with 2.3 patients per 1 million populations in 2014 (the last year for which complete data was available owing to a lag between disease onset and registration). Comparing younger (40-69 years) or older patients (70 years or more), the rate of hPrDs in younger patients was generally stable, but incidence in older patients increased markedly during 1999-2014. The hPrD subtypes included sporadic CJD (n = 2248, 77%), familial CJD (n = 457,16%), Gerstmann-Straussler-Scheinker syndrome (n = 106, 4%), fatal familial insomnia (n = 4), dura mater graft-associated CJD (n = 88, 3%), variant CJD (n = 1), and unclassified CJD (n = 11). 

Conclusions: In Japan, the number of patients with hPrDs tends to increase annually, indicating that older patients with rapidly developing dementia are increasingly being appropriately diagnosed with hPrDs by domestic physicians, supported by the CJD Surveillance Committee. 

PRION 2017  DECIPHERING NEURODEGENERATIVE DISORDERS 

MONDAY, APRIL 27, 2009

The first Japanese patient with variant Creutzfeldt-Jakob disease (vCJD) Case Report


THURSDAY, JANUARY 22, 2015 

Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?


SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Saturday, April 23, 2016 

PRION 2016 TOKYO Saturday, April 23, 2016 

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online Taylor & Francis Prion 2016 Animal Prion Disease Workshop 

Abstracts 

WS-01: Prion diseases in animals and zoonotic potential 

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a, Natalia Fernandez-Borges a. and Alba Marin-Moreno a "Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France 

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier. To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents. These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant. Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.


Title: Transmission of scrapie prions to primate after an extended silent incubation period) *** 

In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 


SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online 



O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 


LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** 




*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, ***

*** and there may be asymptomatic individuals infected with the CWD equivalent. 

*** These circumstances represent a potential threat to blood, blood products, and plasma supplies. 


SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online




why do we not want to do TSE transmission studies on chimpanzees $ 

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis. 

snip... 

R. BRADLEY 


Subject: PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
 
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. 

Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. 

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS

 Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?

IF human transmission studies are unethical and will never take place, how much evidence is enough, and how much exposure do we allow, before a call is made. 

HOW many humans do we expose before enough is enough?

How many body bags now are enough, for a very long incubating disease that the body bags will for sure mount later, if something is NOT finally done NOW.

the public must know.

Now, i will tell you all how this will be interpreted by our fine federal friends, and their lobbyist et al from corporate America, and Doctors there from, here is how this will still read, rubber stamped ;

''There is no direct evidence that CWD can transmit to humans, and CWD has never been identified in humans anywhere in the world, including in areas where CWD has been present in animal populations for decades.''

this is absurd, and fake news at it's finest.

what is 'direct evidence', if human transmission is not possible?

there is more than enough evidence to make that call now. 

with that, who will finally make that judgement call, knowing that if cwd transmits to humans, it will look like the most common human tse prion i.e. sporadic cjd?

who makes that final call, when, and how many more humans must die before that decision is made and put in the public domain so we can go on with this and try to implement rules and regulations that might finally turn the tide, or do just let corporate science run rampant? 

or, will they continue to run with the infamous UKBSEnvCJD only theory$

with cwd now being documented to transmit macaque, AND TO PIGS orally (lot of human medicine made from pigs), the price of continuing to play TSE Prion Poker with humans goes up drastically. 

This is criminal negligence now, imo...terry

*** Subject: CWD TRANSMITS TO MACAQUE ORALLY MUSCLE INTAKE ***

Notice to Members Regarding Chronic Wasting Disease (CWD)

Posted on: May 31st, 2017 

To: MNA Members From: Métis Nation of Alberta 

Date: Wednesday, May 31, 2017 

*** Métis Nation of Alberta (MNA) was made aware of a recent Canadian research study examining the transmission of Chronic Wasting Disease. The initial results of the study indicate that macaque monkeys (genetically similar to humans) can be infected with Chronic Wasting Disease (CWD) after eating deer that is infected with CWD. CWD is a prion disease, which are fatal, transmissible diseases characterized by abnormal proteins in the brain and nervous system. To date no research has shown that CWD can be passed on to humans, and no human cases of CWD have ever been identified. However, this new research indicates that it is a possibility. The Deputy Chief Medical Officer of Health has reached out to us to share with our Métis harvesters this important information. For more information you can visit:


Chronic Wasting Disease: CFIA Research Summary 

 Embargoed until May 23, 2017 

(OCR of a scanned original) 

Research Findings 

Chronic Wasting Disease (CWD) is a progressive, fatal disease of the nervous system of cervids including deer, elk, moose, and reindeer that is caused by abnormal proteins called prions. It is known as a transmissible spongiform encephalopathy (TSE). Other TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans.

A limited number of experimental studies have demonstrated that non-human primates, specifically squirrel monkeys, are susceptible to CWD prions. An ongoing research study has now shown that CWD can also be transmitted to macaques, which are genetically closer to humans. 

The study led by Dr. Stefanie Czub, a scientist at the Canadian Food Inspection Agency (CFIA), and funded by the Alberta Prion Research institute has demonstrated that by orally administering material under experimental conditions from cervids (deer and elk) naturally infected with CWD, the disease can be transmitted to macaques. 

in this project, which began in 2009, 18 macaques were exposed to CWD in a variety of ways: by injecting into the brain, through contact with skin, oral administration, and intravenously (into the bloodstream through veins). So far, results are available from 5 animals. At this point, two animals that were exposed to CWD by direct introduction into the brain, one that was administered infected brain material by oral administration and two that were given infected muscle by oral administration have become infected with CWD. The study is ongoing and testing continues in the remaining animals. The early results will be presented at PRlON 2017, the annual international conference on prion diseases, in Edinburgh, Scotland, May 23 to 26, 2017. 

Potential impacts of the new finding

Since 2003 Canada has a policy that recommends that animals and materials known to be infected with prions be removed from the food chain and from health products. Although no direct evidence of CWD prion transmission to humans has ever been recorded, the policy advocates a precautionary approach to managing CWD and potential human exposure to prions. These initial findings do not change Health Canada’s Health Products and Food Branch (HPFB) position on food and health products. A precautionary approach is still recommended to manage the potential risks of exposure to prions through food and health products. Measures are in place at federal, provincial and territorial levels to reduce human exposure to products potentially contaminated by CWD by preventing known infected animals from entering the marketplace. 

While Federal and P/T government’s animal disease control policies continue to divert known CWD-infected animals away from entering the food and feed supply, research and development of sensitive detection methods including live-animal sampling techniques remain crucial for ensuring an accurate diagnosis. In addition, consistent federal, provincial and territorial communications of appropriate precautionary measures for hunters and indigenous communities are required. 

Next Steps

The CFlA will continue to collaborate with national and international partners to develop and validate new diagnostic techniques. The CFlA will also continue to offer confirmatory testing services and reference laboratory expertise to provincial and territorial partners on demand. 

Currently, CFlA laboratories are leading or collaborating on several research projects to understand the potential for CWD to infect humans. These projects use non‐human primates, genetically modified mice, and cell-free amplification approaches. Given the present findings, CFiA encourages continued research into TSEs. 

The results of this study reinforce the need to redesign the federal program to foster greater adoption of risk mitigation measures for farmed cervids. Federal and provincial government collaboration will continue as new program options are assessed. 

The results of Dr. Czub’s research into CWD will be of interest to scientists, governments, industry and people who consume cervid products. After the presentation at PRION 2017, the research will follow the normal steps of completion, peer review and publication. The Government of Canada will monitor the response to this research and determine whether further review of the science is required. Other studies underway by other researchers may also become public as a result of the presentation of Dr. Czub’s research. 

The Public Health Agency of Canada, Health Canada, CFlA and other Federal partners are working together to assess what policies or programs need further review as well as preparing other communications about the research and health policy and advice to Canadian. 2017/04/28 

===end...UNOFFICIAL...NO URL LINK...TSS===UPDATE, THE ABOVE INTERNAL DOCUMENT HAS NOW BEEN CONFIRMED, but still no link...TSS===

0:30 First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 

Dr Stefanie Czub University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency Canada 


see science to date that the call should be made NOW, that cwd to humans is possible, and all precautions there fore, should be take will great urgency.

WEDNESDAY, MAY 03, 2017

*** First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques


LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***


Molecular Barriers to Zoonotic Transmission of Prions

 *** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 *** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.



*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

you can see more evidence here ;

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1


In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...


snip...see full text ;


Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle... 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells 3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ... 


The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province! ...page 26. 


*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. 


Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1 

Subject: PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh

*see archives of previous Prion Conferences, the ones that are still available, scroll down towards bottom in this link.


I believe that the kind people of Japan consume a great deal of Nutritional Supplements?

SUMMARY Japan represents a challenging, but significant market for U.S. dietary supplements companies. American firms have captured roughly a $500 million share of Japan’s $7.5 billion annual market for these products. Reflecting a trend in recent years of modest market openings achieved through eased regulatory restrictions on dietary supplements, U.S. sales in Japan have been increasing and were up about 5% in 2000. With per capita consumption of dietary supplement by Japanese consumers still only about one-sixth the level found in the United States, the potential for continued growth in this market is enormous, especially as Japan’s aging population turns increasingly to preventative nutritional and healthcare measures. The range of supplement products being marketed in Japan is quite extensive, with over 100 separate products achieving annual sales of at least 500 million yen (US$4.67 million a107 yen/US$). Despite a number of encouraging market trends, the regulatory environment for nutritional supplements in Japan remains opaque and cumbersome. Many products freely sold in others markets must be reformulated before they can be sold in Japan. End of summary. 


Japanese Supplements and Health Food 

Let’s start talking about Japanese supplements with one very important fact – Japanese live the longest in the world with women’s average life expectancy at 87 and men at 80, averaging out at 84. While this achievement is often attributed to Japanese healthy lifestyle and food consumption, the Japanese are also increasingly turning to embrace the magic advancement of health food and dietary supplements. According to Euromonitor International, “value sales of vitamins and dietary supplements are expected to rise at a 1% CAGR at constant 2015 prices over the forecast period to stand at ¥1.2 trillion in 2020”. 

In Japan, the health food and dietary Japanese supplements are booming largely due to the consumption power of the aging population. But, young are not far behind – the beauty and dietary supplements are targeted at those who have little time to eat healthily or hit the gym. Overall, the health food and dietary supplements have become a necessity, thus a hot market, for the Japanese who live in an extremely health, beauty and body conscious society.

In 2010, out of popular 60 health products sold in Japan, the most popular ingredients for dietary supplements:

Collagen (30 products)

Glucosamine (23 products)

Placenta (14 products)

Hyaluronic acid (11 products)

Barley leaf powder (6 products)

Chondroitin sulfate, dietary supplement for treatment of osteoarthritis (5 products)

Blueberry extract (5 products)

Turmeric (5 products)

Another important fact is that the Japanese are also extremely discerning consumers. Who do they trust? What do they take? Below we’ll introduce some of the most popular health food and dietary and beauty supplements in Japan.

1. Collagen Supplements

When it comes to beauty supplements, collagen is the ingredient in Japan. From beauty face masks to seasonings for food, you’ll find it added to almost everything imaginable. The winner of the ongoing collagen war seems to be Shiseido with its tri-series The Collagen, The Collagen Enriched, and The Collagen EX. They offer three types – drinks, tablets and powder. They’ve just introduced its first smoothie powder The Collagen Smoothie, too. Others are not far behind. Food manufacturer giant Meiji is fighting hard with its series Amino Collagen. The product consists of 100% low-molecular fish collagen, which is easily absorbed by the body, at rates 1.5 times greater than pig-skin collagen. Cosmetics giant FANCL goes with apple in its series HTC Collagen DX (powder and tablets). It contains 900mg of collagen in addition to apple polyphenols which help prevent the damage of ultraviolet. DHC offers perhaps the most economical collagen products based on fish collagen peptide and vitamin B1 and B2. 


FDA DOES NOT have mandatory established specifications for animal-derived ingredients to ensure they are BSE free in Nutritional Supplements

''We offer the following comments:  1.    Records must be maintained that demonstrate-that products are not manufactured from, processed with, or does not otherwise contain prohibited cattle materials [21 CFR 189.5(c)(1)]. During the inspection it was determined your firm receives collagen derived from (b)(4) products or by-products; however, your firm was not able to provide any documentation to support the materials are free from bovine spongiform encephalopathy (BSE). Your firm also stated you do not have any established specifications for animal-derived ingredients to ensure they are BSE free.''

WARNING LETTER

CMS#521980 

May 31, 2017
 
VIA UNITED PARCEL SERVICE

DELIVERY SIGNATURE REQUESTED
 
Dr. Caesar DePaco, Owner
Summit Nutritionals International, Inc.
1250 Route 28, Suites 305B, 306 & 308
Branchburg, NJ 08876
 
Dear Dr. DePaco:
 
The U.S. Food and Drug Administration (FDA) inspected your facility located at 1555 Lyell Ave., Rochester, NY 14606-2145, on June 21, 23 and 27, 2016 and again on February 27, 2017 which operates a re-packer of bulk dietary ingredients for your parent frrm, Summit Nutritionals International, Inc., 29 Rockaway Road, Lebanon, NJ, 08833..
 
Our investigator collected receiving records and labeling for your product labeled as Hydrolyzed Salmon Collagen Powder 90% Protein. We have reviewed receiving records and labeling and found violations of the food labeling regulations, 21 CFR Part 101, that cause your product to be misbranded within the meaning of section 403 of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 343]. You can find the Act and FDA’s regulations through links in FDA’s home page at www.fda.gov.
 
Your Hydrolyzed Salmon Collagen Powder 90% Protein product is misbranded within the meaning of Section 403(a)(1) of the Act [21 U.S.C. § 343(a)(1)] in that the product label is false and misleading in any particular. Specifically, during the inspection your product was observed being repackaged and relabeled as Hydrolyzed Salmon Collagen Powder 90% Protein; however, the product is actually Hydrolyzed Gelatin sourced from (b)(4).  Additionally, the manufacturer's label for the Hydrolyzed Gelatin product states that it is "MADE IN CHINA." Whereas the label for the Hydrolyzed Salmon Collagen Powder 90% Protein states that it is "Proudly Made in The USA" and the Certificate of Analysis states "Country of Origin: United States of America" which makes it appear that the country of origin labeling is also false and misleading. Food labeling statements regarding geographical origin must not be false or misleading in any particular. See Compliance Policy Guide (CPG) Sec. 560.200 Country of Origin Labeling for more information at https://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074567.htm
 
We note that additional inspections of your parent firm, Summit Nutritionals International, Inc., 29 Rockaway Road, Lebanon, NJ, 08833 on October 26, 2015 through November 10, 2015 and again on August 15, 2016 through September 13, 2016 also indicated similar misbranding violations may be occurring with your porcine, bovine and/or chicken collagen products. We recommend that you review all of your product labels to be consistent with our policy to avoid additional misbranding of your food products.
 
This letter is not meant to be an all-inclusive list of the violations that exist at your firm or that exist in connection with your products. You are responsible for ensuring that your products are in compliance with the Act and its implementing regulations. You should take prompt action to correct the violations in this letter. Failure to promptly correct the violations may result in enforcement action without further notice, such as seizure or injunction.
 
We offer the following comments:
 
1.    Records must be maintained that demonstrate-that products are not manufactured from, processed with, or does not otherwise contain prohibited cattle materials [21 CFR 189.5(c)(1)]. During the inspection it was determined your firm receives collagen derived from (b)(4) products or by-products; however, your firm was not able to provide any documentation to support the materials are free from bovine spongiform encephalopathy (BSE). Your firm also stated you do not have any established specifications for animal-derived ingredients to ensure they are BSE free. 
 
2.     The product label fails to declare the net quantity of contents as required by 21 CFR 101.7. For example, statements of weight shall be declared in terms of avoirdupois pound and ounce in accordance with 21 CFR 101.7(b)(1).
 
You should respond in writing within fifteen working days from your receipt of this letter outlining the specific steps that you have taken to correct these violations. You should include in your response documentation such as revised product labels and website information, or other useful information that would assist us in evaluating your corrections. If you cannot complete all corrections before you respond, you should explain the reason for your delay and state when you will correct any remaining violations.
 
Section 743 of the Act [21 U.S.C. § 379j-31] authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including re-inspection-related costs. A re-inspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of the Act, specifically to determine whether compliance has been achieved. Re-inspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the re-inspection and assessing and collecting the re-inspection fees [21 U.S.C. § 379j-31(a)(2)(B)]. For a domestic facility, FDA will assess and collect fees for re-inspection-related costs from the responsible party for the domestic facility. The inspection noted in this letter identified noncompliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any re-inspection-related costs. 
 
Your response should be sent to the following address: U.S. Food and Drug Administration, 10 Waterview Blvd., 3rd Floor, Parsippany, New Jersey 07054. If you should have any questions regarding any issue in this letter, please contact Andrew Ciaccia, Compliance Officer.
 
                                                           
Sincerely,
/S/ 
Evelyn Bonnin                                                                                   
Program Division Director
HAF Division 2 E 
 
2017
Page Last Updated: 06/12/2017 

https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm562515.htm

2. Records must be maintained that demonstrate that products are not manufactured from, processed with, or does not otherwise contain prohibited cattle materials [21 CFR 189.5(c)(1)]. During the inspection your firm stated that the soft gel caps used for herbal oil products are derived from bovine products or by-products; however, your firm was not able to provide any documentation to support the materials are free from bovine spongiform encephalopathy (BSE). Your firm also stated you do not have any established specifications for animal-derived ingredients to ensure they are BSE free.

Seattle District Office
22215 26th Ave. SE, Ste. 210
Bothell, WA 98021
 
November 15, 2016
 
OVERNIGHT DELIVERY
SIGNATURE REQUIRED
 
In reply refer to Warning Letter SEA 17-02
 
Raymond W. Szeto, President
NutriResearch, Inc.
704 West Meeker Street
Kent, Washington 98032-5758
 
WARNING LETTER
 
Dear Mr. Szeto:
 
The United States Food and Drug Administration (FDA) conducted an inspection of your facility located at 704 West Meeker Street, Kent, Washington, on March 24, 25, and 29, 2016, and April 5 and 15, 2016. During the inspection we collected labeling for your products. Based on our inspection and subsequent review of your firm’s labeling, we found serious violations of the Federal Food, Drug and Cosmetic Act (the Act) and applicable regulations. You can find the Act and FDA’s regulations through links on FDA’s home page at www.fda.gov.
 
Unapproved New Drugs/Misbranded Drugs
 
The FDA reviewed your website at the Internet address www.biomedbalance.com in November 2016 and determined that you take orders there for the products Chaga, Eye Health, Hepatocel Plus, Reishi, Coriolus, Healthy Joint, Horny Goat Weed, and GlucoResistance.  In addition, the FDA reviewed some of your product labels and your “BioMed Balance Beauty Naturally A Division of NutriResearch Inc pamphlet” that you include in product shipments to customers.  The claims on your product labels and website and in your pamphlet establish that these products are drugs under section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)] because they are intended for use in the cure, mitigation, treatment, or prevention of disease. As explained further below, introducing or delivering these products for introduction into interstate commerce for such uses violates the Act. 
 
Examples of some of the claims that provide evidence that your products are intended for use as drugs include:
 
Chaga

Website:

“[B]een used . . . as a cleansing and disinfecting measures and as decoctions for stomach diseases, intestinal worms liver and heart ailments and cancer treatments . . . Chaga has demonstrated anti-HIV, antibacterial anti-malarial, anti-inflammatory and anthelmintic properties.” 

Eye Health

Website:

“[S]upports eye conditions such as Cataract, Glaucoma, age related Macular Degeneration, dry eyes . . .” 

Hepatocel Plus

Website:

“[D]eveloped to target Hepatitis C virus in three ways: first . . . it destroys HCV-RNA* and prevented HCV from replicating further; second, it modulates the immune system to produce antibodies against HCV and stimulate Macrophage, Natural Killer Cell, Neutrophil and T-Lymphocytes*, protects liver cells by lowering the serum glutamic pyruvate transaminase (SGPT) in patients with HCV, both SGOT and SGPT are used to monitor liver inflammation*, also . . . ability to reduce hepatocellular necrosis which, in turn, may delay or prevent the occurrence of hepatic (liver) failure*.”

Pamphlet:

“[D]estroys HCV-RNA* and prevented HCV from replicating further . . . modulates the immune system to produce antibodies against HCV and stimulate Macrophage, Natural Killer Cell, Neutrophil and T-Lymphocytes* . . . protects liver cells by lowering the serum glutamic pyruvate transaminase (SGPT) in patients with hepatic (liver) failure.”
 
Reishi

Pamphlet:

“Reishi has a cure rate as impressive as that treat [sic] by pharmacology . . . ability to treat numerous health problems, from high blood pressure to AIDS . . . Reishi eliminates cholesterol build-up . . . Reishi is a natural anticoagulant . . .”

“Testimony No. 2: Cold & Flu and the New Miracle Cure…abscess tooth . . . medicine helped reduce the swelling and pressure . . . our new miracle cure for everything.”

“Testimony No. 3: Bronchitis . . . ReishiGold after I took it.  I got rid of my bronchitis in 2 days.”

“Testimony No. 5: Brain tumor shrink, healed toothache. . . ResishiGold . . . think helped his tumor shrink some per his CAT scans . . .”

“Testimony No. 10: Diabetes: After (take ReishiGold) one week need for insulin dropped 30% . . .”
 
Coriolus

Pamphlet:

“[I]n Japan and China, Coriolus is widely used as prescription medicines for treatment of cancer . . . anti-tumor effect have been reported . . . increase survival rates . . . proved to [sic] effective against tumor both in animal experiments and in clinical patients.”
 
Healthy Joint

Website:

“E]ffective for the treatment of arthritis pain, muscular spasm, nerve pain and ligament strain and sprain . . . effective as an analgesic, anti-inflammatory and sedative agent similar to nonsteroidal anti-inflammatory drugs (NSAIDS) in the treatment of arthritis . . .  helps increase the release of dopamine level in the body and brain to act as a natural pain reliever . . . useful in the treatment of Rheuma- toid [sic] arthritis and Osteoarthritis. Collagen helps with the healing and repairing damaged bones and cartilages.”

Pamphlet:

“[E]ffective for the treatment of arthritis pain, muscular spasm, nerve pain and ligament strain and sprain . . . effective as an analgesic, anti-inflammatory and sedative agent similar to nonsteroidal anti-inflammatory drugs (NSAIDS) in the treatment of arthritis . . . helps increase the release of dopamine level in the body and brain to act as a natural pain reliever . . . useful in the treatment of Rheuma- toid [sic] arthritis and Osteoarthritis. Collagen helps with the healing and repairing damaged bones and cartilages.”
 
Horny Goat Weed

Pamphlet:

“[H]elp treat chronic bronchitis, Asthma, neurological and immunological inhitition [sic], cardio-cerebral vascular disease, cerebral asteriosclerosis and coronary heart disease . . . used to treat high blood pressure in elderly women, paralysis of the lower limbs.  It has also use for depression . . .”
 
GlucoResistance

Pamphlet and website:

“[L]owers blood glucose . . . helps human insulin to become more sensitive for the uptake of glucose into the cells . . . improve cholesterol profiles, to combat obesity and hyperglycemia.”
 
Healthy Vision (Teresa Charities brand)

Product Label:

“Healthy Vision nutritional formula supports eye conditions such as Cataract, Glaucoma, Age-Related Macular Degeneration, dry eyes . . .”
The products listed above are not generally recognized as safe and effective for the above referenced uses and, therefore, the products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 321(d) and 355(a)]. FDA approves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that the drug is safe and effective.
 
A drug is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] if the drug fails to bear adequate directions for its intended use(s).  “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1)(A) of the Act [21 U.S.C. § 353(b)(1)(A)], can only be used safely at the direction, and under the supervision, of a licensed practitioner.
 
Your products Chaga, Eye Health, Hepatocel Plus, Reishi, Coriolus, Horny Goat Weed, GlucoResistance, and Healthy Vision are intended for treatment of one or more diseases that are not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use your products safely for their intended purposes. Accordingly, Chaga, Eye Health, Hepatocel Plus, Reishi, Coriolus, Horny Goat Weed, GlucoResistance, and Healthy Vision fail to bear adequate directions for their intended use and, therefore, the products are misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)].  The introduction or delivery for introduction into interstate commerce of these misbranded drugs violates section 301(a) of the Act [21 U.S.C. § 331(a)].
 
Dietary Supplement CGMP Violations
 
Our investigators observed the following significant violations of FDA’s Current Good Manufacturing Practice (CGMP) requirements for dietary supplements, Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111), which render your Cordyceps Sinensis and Red Cordyceps Extract products adulterated under section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)]. Additionally, even if your Healthy Vision product did not have therapeutic claims which make it an unapproved new drug and misbranded drug, Healthy Vision would be an adulterated dietary supplement under section 402(g)(1) of the Act [21 U.S.C. § 342(g)(1)] for the reasons described below. 
 
The following observations were noted on the Form FDA 483, Inspectional Observations, issued to you on April 15, 2016. We received your response dated April 25, 2016, and have addressed relevant information from your response below.  

You failed to establish and follow written procedures to fulfill the requirements relating to product complaints, as required by 21 CFR 111.553.  Specifically, your firm has not established written procedures for the review and investigation of product complaints.  Once you establish the required written procedures relating to product complaints, you must make and keep a written record of every product complaint that is related to good manufacturing practice, in accordance with 21 CFR 111.570(b)(2).

We have reviewed your response letter dated April 25, 2016, and find your response to be inadequate because the written procedure you provided fails to establish written procedures that fulfill the requirements applicable to the review and investigation of product complaints. Specifically, your written procedure fails to designate a qualified person to review all product complaints to determine whether the product complaint involves a possible failure of a dietary supplement to meet any of its specifications, and your procedure does not require that quality control personnel must review and approve decisions about whether to investigate a product complaint, in accordance with 21 CFR 111.560.  

You failed to establish the required specifications for points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record (MMR), as required by 21 CFR 111.70(a).  You do not have written specifications to ensure the consistent production of your finished dietary supplements.  Specifically, for your Healthy Vision, Lot # 5120, Cordyceps Sinensis, Lot # 7177, and/or Red Cordyceps Extract Lot # 6204 and 6205 products: 

a.  You failed to establish the following required component specifications for each component that you use in the manufacture of a dietary supplement:
 
i.  Identity specifications [21 CFR 111.70(b)(1)];

ii.  Component specifications that are necessary to ensure that specifications for the purity, strength, and composition of dietary supplements manufactured using the components are met [21 CFR 111.70(b)(2)]; and

iii.  Limits on those types of contamination that may adulterate or may lead to adulteration of the finished batch of the dietary supplement to ensure the quality of the dietary supplement [21 CFR 111.70(b)(3)].
 
b.  You failed to establish in-process specifications for any point, step, or stage in the MMR where control is necessary to help ensure that specifications are met for the identity, purity, strength, and composition of the dietary supplements and, as necessary, for limits on those types of contamination that may adulterate or may lead to adulteration of the finished batch of the dietary supplement, as required by 21 CFR 111.70(c)(1).
 
c.  You failed to establish specifications for dietary supplement labels (label specifications) and for packaging that may come in contact with dietary supplements (packaging specifications), as required by 21 CFR 111.70(d).
 
d.  You failed to establish product specifications for the identity, purity, strength, and composition of the finished batch of the dietary supplement, and for limits on those types of contamination that may adulterate, or that may lead to adulteration of, the finished batch of the dietary supplement to ensure the quality of the dietary supplement, as required by 21 CFR 111.70(e).
 
Once you have established the required specifications, you must verify that the specifications are met, in accordance with 21 CFR 111.73.
 
We have reviewed your response letter dated April 25, 2016. We are unable to evaluate the adequacy of your corrective action because you failed to provide specific information to demonstrate that you have established the required specifications, as identified in 21 CFR 111.70.

You failed to prepare and follow a written MMR for each unique formulation of dietary supplement that you manufacture, and for each batch size, to ensure uniformity in the finished batch from batch to batch, as required by 21 CFR 111.205(a).  For example, during the inspection, the investigators observed that you had not prepared MMRs for the following dietary supplements: 

a.    Healthy Vision, Lot # 5120

b.    Cordyceps Sinensis, Lot # 7177

c.    Red Cordyceps Extract, Lot # 6204 and 6205
 
We have reviewed your response letter dated April 25, 2016, but we are unable to evaluate the adequacy of your corrective action because the information you provided does not demonstrate that you have prepared MMRs for your Healthy Vision and Red Cordyceps Extract products that satisfy the requirements of 21 CFR 111.205(a).  Additionally, while it appears that you attached a document titled Exhibit A for the purpose of demonstrating the MMR you intend to use for your Cordyceps Sinensis product, this document is inadequate for use as an MMR because it does not contain the following information, as required by 21 CFR 111.210. Specifically, it fails to contain:
 
a.    A complete list of components to be used [21 CFR 111.210(b)];

b.    An accurate statement of the weight or measure of each component to be used [21 CFR 111.210(c)];

c.    A statement of any intentional overage amount of a dietary ingredient [21 CFR 111.210(e)];

d.    A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finish manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made [21 CFR 111.210(f)];

e.    A description of packaging [21 CFR 111.210(g)]; and

f.     Written instructions of specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled, as specified in the MMR [21 CFR 111.210(h)(1)].
 
4.    You failed to prepare a batch production record (BPR) every time you manufactured a batch of dietary supplement, as required by 21 CFR 111.255(a). Specifically, you do not prepare a BPR as part of your production process.
 
We have reviewed your response letter dated April 25, 2016, but we are unable to evaluate the adequacy of your corrective action. In your response you provided a document titled Exhibit A for the purpose of demonstrating the MMR you intend to use to comply with MMR requirements, and your response asserts that the same document will be used “to comply the batch production record every time we manufactured a batch of dietary supplement.”However, the document provided does not include all information required as part of a BPR. Example of some of the missing information includes the identity of equipment and processing lines used in producing the batch; the date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in the production of the batch; the unique identifier that you assign to each component; and the identity and weight or measure of each components used (21 CFR 111.260). 
You failed to establish and follow written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any processing, as required by 21 CFR 111.103. Specifically, you have not established any quality control procedures.  

Once you have established your written quality control procedures, you must implement quality control operations in your manufacturing, packaging, labeling, and holding operations for producing the dietary supplement to ensure the quality of the dietary supplement, as required by 21 CFR 111.65.
 
We have reviewed your response letter dated April 25, 2016, but we are unable to evaluate the adequacy of your corrective action. Your response asserts that you have established written procedures for quality control to meet the identity, purity, strength, and composition of the finished products, but the documentation you provided with your response does not include written procedures for quality control operations that include actions for conducting a material review, making a disposition decision, and approving or rejecting any reprocessing. 

You failed to establish and follow written procedures for returned dietary supplements, as required by 21 CFR 111.503. Specifically, you do not have written procedures for returned dietary supplements. During our inspection, our investigators observed returned products that were held in a small room at the back of your processing facility. These dietary supplements were not clearly identified as returned products and were not held or tagged to preclude redistribution. The investigators observed one box containing 36 bottles of unlabeled dietary supplements, along with returned boxes of dietary supplements with 2018 and 2019 expiration dates. 

We have reviewed your response letter dated April 25, 2016, but we are unable to evaluate the adequacy of your corrective action. Your response states that you have established written procedures for certain situations in which dietary supplements are returned, but your response does not provide written procedures establishing the storage, tracking, and disposition of returned product. In addition, you did not advise what, if anything, you have done with the returned products our investigators observed during the inspection.  

You failed to establish and follow written procedures for fulfilling the requirement for equipment and utensils, including written procedures for calibrating instruments and controls that you use in manufacturing or testing a component or dietary supplement, as required by 21 CFR 111.25(a).  Specifically, you have not established a written accuracy check or calibration procedure for your floor and desktop scales. 
We have reviewed your response letter dated April 25, 2016, but we are unable to evaluate the adequacy of your corrective action. Your response stated that you have established written procedures for calibrating floor and desktop weighing scales, but you provided no documentation to demonstrate whether and how such procedures have been established. 

You failed to use equipment and utensils that are of appropriate design, construction, and workmanship to ensure them to be suitable for their intended use and to be adequately cleaned and properly maintained, as required by 21 CFR 111.27(a). Specifically, we observed white labels covering various holes of the capsule counting machine.  These labels are moved depending on the desired number of capsules per bottle and appear to leave a residue behind after they are removed.  We observed this machine being utilized in counting “Healthy Vision” capsules on March 24 and 25, 2016, prior to bottling.

You failed to establish and follow written procedures for packaging and labeling operations, as required by 21 CFR 111.403. Specifically, you have not established written procedures for labeling operations, and the labeling operations observed during the inspection identified significant discrepancies between your formula worksheet and the product label for your Healthy Vision, Cordyceps Sinensis, and Red Cordyceps Extract.  

Once you have established the required procedures, you must establish, before packaging and labeling, packaging and labels for each batch of dietary supplement to determine whether the packaging and labels conform to the MMR, as required by 21 CFR 111.410(c). 
 
Adulterated Dietary Supplement
 
Additionally, even if your Healthy Vision product did not have therapeutic claims which make it an unapproved new drug and misbranded drug, the product would be adulterated under section 402(c) of the Act [21 U.S.C. § 342(c)] because the product bears or contains color additives which are unsafe within the meaning of section 721(a) of the Act [21 U.S.C. § 379(a)].  Subject to limited exceptions, section 721(a) deems a color additive to be unsafe unless its use is in conformity with the color additive's listing regulation.  Specifically, your Healthy Vision product declares Astaxanthin and Anthocyanins on the product label, which are not approved for use as color additives as they are used in this product.
 
Misbranded Dietary Supplements 

Your Healthy Vision, Cordyceps Sinensis, and Red Cordyceps Extract products are misbranded within the meaning of section 403(e)(1) of the Act [21 U.S.C. § 343(e)(1)] in that the labels fail to list the name and place of business of the manufacturer, packer, or distributor.  Specifically, the statement of the place of business fails to include the city for the Red Cordyceps Extract product and the zip code for all three products, in accordance with 21 CFR 101.5(d).

Your Healthy Vision, Cordyceps Sinensis and Red Cordyceps Extract products are misbranded within the meaning of section 403(s)(2)(C) of the Act [21 U.S.C. § 343(s)(2)(C)] in that the labels fail to identify the part of the plant (e.g., root, leaves) from which each botanical dietary ingredient in the product is derived, as required by 21 CFR 101.4(h)(1). For example,

a.  Your Healthy Vision product label fails to include the part of the plant from which Sabucus Nigra Extract is derived.

b.  Your Cordyceps Sinensis and Red Cordyceps Extract product labels fail to include the part of the plant from which the cordyceps sinensis extract is derived.

Your Cordyceps Sinensis and Red Cordyceps Extract products are misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2)] in that the product labels fail to declare all the common or usual names of each ingredient used, as required by 21 CFR 101.36 and 21 CFR 101.4.  For example,

a.  The Cordyceps Sinensis and Red Cordyceps Extract product labels declare “Polysaccharide” and “Polysaccharides”, respectively, but fail to list the name of the individual Polysaccharide(s).

b.  The Red Cordyceps Extract product label declares “S.B. Extract” but fails to list the common or usual name of this ingredient.

c.  The Cordyceps Sinensis and Health Vision product labels indicate vegetarian capsules.  However, the labels fail to declare the capsule ingredients.
 
4.    Your Red Cordyceps Extract product is misbranded within the meaning of sections 403(s)(2)(A)(ii)(I) and 403(q)(5)(F) of the Act [21 U.S.C. §§ 343 (s)(2)(A)(ii)(I) and 343(q)(5)(F)] in that it fails to include the quantitative amount by weight per serving size of all the dietary ingredients as required by 21 CFR 101.36.  Specifically, the product label fails to include the quantitative amount by weight of Standardized Polysaccharides; as noted previously, this ingredient must be listed by the common or usual name.  We also note that if the “Standardized Polysaccharides” constituents of the Cordyceps Sinensis Extract product, then the common or usual name of the “Standardized Polysaccharides” should be indented under “Cordyceps Sinensis Extract” with the quantitative amount per serving.

Your Healthy Vision product is misbranded within the meaning of section 403(q)(5)(F) of the Act [U.S.C. § 343(q)(5)(F)] in that the label fails to declare Vitamin C in accordance with 21 CFR 101.36(c)(1).  This dietary ingredient contained in the proprietary blend must be declared in accordance with 21 CFR 101.36(b)(2) and dietary ingredients contained in the proprietary blend that are listed under 21 CFR 101.36(b)(3) are to be indented under the term “Proprietary Blend” and listed under the column of names described in 21 CFR 101.36(b)(2)(i)(B).
Your Healthy Vision and Cordyceps Sinensis products are misbranded within the meaning of 403(s)(2)(B) of the Act [21 U.S.C. § 343(s)(2)(B)] in that the labels do not include a statement of identity as a “dietary supplement” as required by 21 CFR 101.3(g).

Your Red Cordyceps Extract dietary supplement product is misbranded within the meaning of section 403(y) of the Act [21 U.S.C. § 343(y)], in that the label fails to include a domestic address or domestic phone number through which    the responsible person, as described in section 761(b) of the Act [21 U.S.C §379AA-1], may receive a report of a serious adverse event with such dietary supplement.
This letter is not intended to be an all-inclusive list of the violations that exist in connection with your products.  You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations.  It is your responsibility to ensure that your firm complies with the Act and FDA regulations.
 
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations and implement lasting corrective action of these violations may result in regulatory action without further notice, including, without limitation, seizure and injunction.
 
We offer the following comments:
 
1. Any expiration date, shelf life, or “Best by” date you place on a product label should be supported by stability data [72 Fed. Reg. 34752, 34856 (Jun. 25, 2007)].  The term “shelf life dating” includes expiration dating and “best if used by” dating [72 Fed. Reg. 34752, 34912 (Jun. 25, 2007)].  You informed our investigator that you use expiration dates on your finished product labels; however, you did not have stability testing data to support this date.
 
2.  Records must be maintained that demonstrate that products are not manufactured from, processed with, or does not otherwise contain prohibited cattle materials [21 CFR 189.5(c)(1)].  During the inspection your firm stated that the soft gel caps used for herbal oil products are derived from bovine products or by-products; however, your firm was not able to provide any documentation to support the materials are free from bovine spongiform encephalopathy (BSE). Your firm also stated you do not have any established specifications for animal-derived ingredients to ensure they are BSE free.
 
Please notify this office in writing within fifteen business days from the date you receive this letter describing the specific steps you have taken to correct the noted violations and to prevent these violations, or other similar violations, from occurring again. You should include documentation of corrective actions you have taken to date. If your firm’s planned corrections will occur over time, please state the reason for the delay and include a timetable for implementation of those corrections.
 
Section 743 of the Act (21 U.S.C. 379j-31) authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including reinspection-related costs. A reinspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of the Act, specifically to determine whether compliance has been achieved. Reinspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the reinspection and assessing and collecting the reinspection fees [21 U.S.C. 379j-31(a)(2)(B)]. For a domestic facility, FDA will assess and collect fees for reinspection-related costs from the responsible party for the domestic facility. The inspection noted in this letter identified noncompliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any reinspection-related costs.
 
Your reply should be sent to: U.S. Food and Drug Administration, 22215 26th Avenue SE, Suite 210, Bothell, Washington 98021, to the attention of Patricia A. Pinkerton, Compliance Officer. Refer to the identification number WL SEA 17-02 when replying. If you have any questions regarding any issues in this letter, please contact Compliance Officer Patricia Pinkerton by telephone at 425-302-0428. 
 
Sincerely,
/S/ 
Miriam R. Burbach
District Director
 
cc: Washington State Department of Agriculture
Food Safety Program
P.O. Box 42560
Olympia, Washington 98504-2560


*** unbelievable, absolutely unbelievable that this is still going on in 2017. please remember, some 300,000 cattle in the UK died from mad cow disease due to nothing more than a crude nutritional supplement called CATTLE FEED. ...terry

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Location: Virus and Prion Research

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin

Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). Conclusions:

This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.

CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.

Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...


 we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.


 Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....


 snip...see much more here ;

WEDNESDAY, APRIL 05, 2017

Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease


TUESDAY, APRIL 18, 2017 

*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***


MONDAY, JUNE 19, 2017 

FDA DOES NOT have mandatory established specifications for animal-derived ingredients to ensure they are BSE free in Nutritional Supplements



Terry S. Singeltary

posted by Terry S. Singeltary Sr. at 11:40 AM